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US20070116745A1 - Spermicidal preparations and uses thereof - Google Patents

Spermicidal preparations and uses thereof Download PDF

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Publication number
US20070116745A1
US20070116745A1 US10/590,070 US59007005A US2007116745A1 US 20070116745 A1 US20070116745 A1 US 20070116745A1 US 59007005 A US59007005 A US 59007005A US 2007116745 A1 US2007116745 A1 US 2007116745A1
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US
United States
Prior art keywords
copper silicate
contraceptive
sperm
copper
silicate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/590,070
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English (en)
Inventor
John Dawson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Conve Ltd
Original Assignee
Conve Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from AU2004900719A external-priority patent/AU2004900719A0/en
Application filed by Conve Ltd filed Critical Conve Ltd
Assigned to CONVE LTD. reassignment CONVE LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DAWSON, JOHN
Publication of US20070116745A1 publication Critical patent/US20070116745A1/en
Abandoned legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/34—Copper; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/16—Masculine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives

Definitions

  • the present invention relates to the use of copper silicate compositions active against sperm and in particular compositions that are able to kill and/or retard sperm motility.
  • the present invention also relates to contraceptive compositions comprising copper silicate adapted for topical administration.
  • the present invention also relates to contraceptive devices impregnated or otherwise treated to contain copper silicate.
  • spermicides exert an anti-fertility effect upon spermatozoa as it passes through the female genital tract.
  • a compound must meet essential requirements. It must act rapidly and efficiently to kill or immobilize sperm on contact, or render sperm incapable of fertilization. It also should (i) be suitable for administration in terms of not being unduly irritating to the vaginal and penile mucosa (ii) not have any adverse effect on a developing embryo or fetus, and (iii) be free of long-term toxicity. Moreover, it should be systemically non-toxic.
  • spermicidal contraceptives have detergent ingredients that disrupt cell membranes (due to their affinity to the membrane lipids). These include the neutral surfactants nonoxynol-9 (N-9), menfegol, and octoxynol-9 (O-9). N-9 is the most commonly used spermicidal contraceptive in the UK and the USA. The cationic surfactant benzalkonium chloride and the anionic detergent sodium docusate are also used worldwide as vaginal spermicides. Octoxynol-9 is currently the only neutral surfactant present on the Australian market. Its properties are presented as equivalent to that of N-9.
  • the present invention seeks to overcome the above problems by providing safe and effective sperm-active compositions, including topical formulations that can be used to control sperm.
  • the present invention provides a method of controlling sperm, the method comprising the step of contacting the sperm with an effective amount of copper silicate.
  • the ability of copper silicate to control sperm renders it useful in applications where it is desirous to reduce or totally remove sperm motility or otherwise inactivate sperm.
  • One particular application where this activity is useful is in the production of contraceptives.
  • the present invention also provides for the use of an effective amount of copper silicate as a contraceptive.
  • the copper silicate used in the methods of the present invention may be formulated to render them particularly suitable for administration to mammals such as humans.
  • the present invention also provides for the use of copper silicate for the preparation of a formulation for use as a contraceptive and a composition adapted for topical administration comprising an effective amount of copper silicate wherein the effective amount is sufficient to act as a contraceptive.
  • the copper silicate used in the method of the present invention may also be combined or otherwise integrated into existing contraceptive devices such as barrier agents to improve their effectiveness as a contraceptive.
  • the present invention also provides a contraceptive device comprising copper silicate.
  • the present invention provides a method of controlling sperm, the method comprising the step of contacting the sperm with an effective amount of copper silicate.
  • controlling sperm and similar phrases such as “controls sperm” means one or more of the following: at least reducing sperm motility, at least reducing the number of viable sperm, at least reducing the ability to penetrate cervical mucous and killing sperm.
  • the ability of copper silicate to control sperm renders it useful as a contraceptive.
  • the present invention also provides for the use of an effective amount of copper silicate as a contraceptive.
  • the copper silicate When used as a contraceptive the copper silicate may be applied in a variety of ways so that it contacts and controls the sperm.
  • the copper silicate may be applied to a site expected to receive or come into contact with sperm.
  • the site may be a body part such as a reproductive organ or part thereof and in particular the site may be part of the reproductive tract, the penis, vagina or cervix.
  • the site may be a physical object such as another contraceptive agent such as a condom, diaphragm or the like or a sex aid.
  • the effective amount of the copper silicate applied in the method of the present invention will vary depending, at least, on the application site and the conditions at that site. However, it will at least be sufficient to control sperm.
  • Examples of the amount of copper silicate product applied according to the method of the present invention are weight range: 1-10 g, 2-8 g or 4-6 g.
  • the frequency with which, and the duration for which, the copper silicate is applied will be sufficient to control sperm and thus will also vary depending at least on the site of application and the concentration of the copper silicate. It is expected the copper silicate will be applied on a needs basis by the end user to meet specific requirements.
  • the copper silicate used in the methods of the present invention may be specially formulated.
  • the present invention also provides for the use of copper silicate for the preparation of a formulation for controlling sperm or use as a contraceptive.
  • the formulations of the present invention may be produced by dissolving or combining the copper silicate in an aqueous or non-aqueous carrier.
  • an aqueous or non-aqueous carrier In general, any liquid, cream, or gel, or similar substance that does not appreciably react with the copper silicate or any other active ingredient that may be introduced and which is non-irritating is suitable.
  • the formulations may be adapted for administration via a range of routes. However, preferably, the formulations are adapted for topical administration.
  • the present invention also provides, a method of producing a compound adapted for topical administration comprising the step of dissolving or combining copper silicate in an aqueous or non-aqueous topical carrier.
  • the present invention also provides a formulation adapted for topical administration comprising an effective amount of copper silicate.
  • topical means application to a localized area of the body and/or to the surface of a body part and includes administration to the vagina (such as intra-vaginally) and to the mucous membranes.
  • the form of the copper silicate in the formulation of the present invention may be varied provided it retains its ability to control sperm.
  • the copper silicate is present in the formulation as a solution.
  • Acidified solutions, including aqueous solutions, are particularly preferred because copper silicate is more soluble and stable at acidic pH.
  • Particularly preferred pHs are 3-6, 4-6 and 5-6.
  • the pH of the formulation should be physiologically acceptable.
  • the formulations may be rendered acidic through the addition of acids that are therapeutically acceptable in terms of not unduly comprising the effectiveness of the formulation by being overly irritating or causing other undesirable side-effects.
  • a particularly preferred therapeutically acceptable acid for the purposes of the present invention is acetic acid.
  • the final concentration of acetic acid in the formulations of the present invention may be varied and preferably are between about 0.1% wt and 2% wt and more preferably 0.5% wt and 1.5% wt.
  • the copper silicate may also be in solid form provided it is properly prepared.
  • the copper silicate could be in the form of a micronized solid such as chrysocolla.
  • composition adapted for topical administration may be in the form of any one of the following: solution, lotion, suspension, emulsion, cream, gel, ointment, liniment and salve. Particularly preferred forms are ointments, creams or gels.
  • Ointments generally are prepared using either (1) an oleaginous base, i.e., one consisting of fixed oils or hydrocarbons, such as white petroleum or mineral oil, or (2) an absorbent base, i.e., one consisting of an anhydrous substance or substances that can absorb water, for example anhydrous lanolin.
  • an oleaginous base i.e., one consisting of fixed oils or hydrocarbons, such as white petroleum or mineral oil
  • an absorbent base i.e., one consisting of an anhydrous substance or substances that can absorb water, for example anhydrous lanolin.
  • the active ingredient is added to an amount affording the desired concentration.
  • Creams are oil/water emulsions. They consist of an oil phase (internal phase), comprising typically fixed oils, hydrocarbons and the like, waxes, petroleum, mineral oil and the like and an aqueous phase (continuous phase), comprising water and any water-soluble substances, such as added salts.
  • the two phases are stabilised by use of an emulsifying agent, for example, a surface active agent, such as sodium lauryl sulfate; hydrophilic colloids, such as acacia colloidal clays, veegum and the like.
  • the compound may be added to the water phase prior to formation of the emulsion, in an amount to achieve the desired concentration.
  • Gels comprise a base selected from an oleaginous base, water, or an emulsion-suspension base.
  • a gelling agent that forms a matrix in the base, increasing its viscosity.
  • gelling agents are hydroxypropyl cellulose, acrylic acid polymers and the like.
  • the compound may be added to the formulation at the desired concentration at a point preceding addition of the gelling agent.
  • the formulations of the present invention have lubricant characteristics.
  • the present invention also provides a formulation adapted for topical administration comprising an effective amount of copper silicate wherein the formulation is adapted to also act as a lubricant.
  • the formulations of the present invention will often have lubricant characteristics inherently due to other agents in the formulation. However, this aspect of the invention also covers lubricants that have copper silicate incorporated therein.
  • the formulations of the present invention may further comprise an auxiliary agent such as any one or more of: preservatives, stabilizers, emulsifiers, wetting agents, fragrances, colouring agents, odour controllers and thickeners such as natural gums.
  • an auxiliary agent such as any one or more of: preservatives, stabilizers, emulsifiers, wetting agents, fragrances, colouring agents, odour controllers and thickeners such as natural gums.
  • the concentration of the copper silicate in the formulation may be varied as required and with reference to the intended end use. However, preferably, the concentration of the copper silicate is such that its final concentration is approximately 0.01% -10% w/w (as Cu). More preferably, the concentration of the copper silicate is to a final concentration of approximately 0.05% -0.5% w/w (as Cu) or 0.05% -0.3% (as Cu).
  • the formulations of the present invention include those that are adapted for delivery via a solid dosage form such as a tablet or suppository.
  • a solid dosage form such as a tablet or suppository or the like comprising copper silicate or a formulation thereof.
  • Solid dosage forms suitable for the purposes of the present invention are described generally in Martin, Remington's Pharmaceutical Sciences, 18th Ed. (1990 Mack Publishing Co. Easton Pa. 18042) which is herein incorporated by reference. These include tablets, capsules and pellets.
  • Disintegrants may be included in the solid dosage form.
  • Materials used as disintegrants include but are not limited to starch including the commercial disintegrant based on starch, Explotab. Sodium starch glycolate, Ambedite, sodium carboxymethylcellulose, ultramylopectin, sodium alginate, gelatine, orange peel, acid carboxymethyl cellulose, natural sponge and bentonite may all be used.
  • Another form of the disintegrants are insoluble cationic exchange resins. Powdered gums may be used as disintegrants and as binders and these can include powdered gums such as agar, Karaya or tragacanth. Alginic acid and its sodium salt are also useful as disintegrants.
  • Lubricants may be used as a layer between the copper silicate and the die wall and these can include but are not limited to: stearic acid including its magnesium and calcium salts, polytetrafluoroethylene (PTFE), liquid paraffin, vegetable oils and waxes. Soluble lubricants may also be used such as sodium lauryl sulfate, magnesium lauryl sulfate, polyethylene glycol of various molecular weights and Carbowax 4000 and 6000.
  • the glidants may include starch, talc, pyrogenic silica and hydrated silicoaluminate.
  • a surfactant might be added as a wetting agent.
  • Surfactants may include anionic detergents such as sodium lauryl sulfate, dioctyl sodium sulfosuccinate and dioctyl sodium sulfonate.
  • anionic detergents such as sodium lauryl sulfate, dioctyl sodium sulfosuccinate and dioctyl sodium sulfonate.
  • Cationic detergents might be used and could include benzalkonium chloride or benzethomium chloride.
  • nonionic detergents that could be included in the formulation as surfactants are lauromacrogol 400, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil 10, 50 and 60, glycerol monostearate, polysorbate 40, 60, 65 and 80, sucrose fatty acid ester, methyl cellulose and carboxymethyl cellulose. These surfactants could be present in the formulation of the compositions either alone or as a mixture in different ratios.
  • Controlled release formulations may be desirable.
  • the compositions could be incorporated into an inert matrix that permits release by either diffusion or leaching mechanisms such as gums.
  • Slowly degenerating matrices may also be incorporated into the formulation.
  • Another form of a controlled release is by a method where the copper silicate is enclosed in a semipermeable membrane that allows water to enter and push the copper silicate out through a single small opening due to osmotic effects. Some enteric coatings also have a delayed release effect.
  • Film coating may be carried out in a pan coater or in a fluidised bed or by compression coating.
  • the copper silicate can also be included in the formulation as multiparticulates such as granules or pellets of particle size about 1 mm.
  • the invention further provides for formulations comprising microparticles, created from hydrophilic polymers, which contain copper silicate.
  • the microparticles containing the copper silicate may be made by a variety of methods known to those in the art, for example, solvent evaporation, desolvation, complex coacervation, polymer/polymer incompatibility and interfacial polymerisation.
  • the copper silicate may also be incorporated into or applied to other contraceptive devices such as barrier agents to improve their contraceptive capacity.
  • the present invention also provides a contraceptive device comprising copper silicate.
  • the devices of the present invention may be varied provided they are adapted to receive or be treated in a fashion that enables them to incorporate copper silicate and later make the copper or copper silicate bioavailable in a manner that enables it to control sperm.
  • the device is a barrier agent such as an agent selected from the group consisting of: sponges, films, cervical caps, diaphragms and condoms.
  • the copper silicate When the copper silicate is incorporated into a device it may be incorporated into the matrix of the material from which the device is made or it may be applied as a coating on the device. This may be relatively simple in the case of a sponge. However, when the device is a condom incorporating the copper silicate into the rubber matrix may involve some trial and error to ensure the copper is bioavailable. Regardless, armed with the information herein a person skilled in the art can produce the devices of the present invention through routine trial and experiment.
  • CSSOL1 Ingredient % wt CSC 25.22 Water 74.73 Sodium alkyl ether sulfate 0.05
  • the assessment of the effect of the spermicides tested (copper silicate or “reference” spermicide—Octoxinol-9) was conducted against the untreated sperm.
  • spermicides tested copper silicate or “reference” spermicide—Octoxinol-9
  • All spermicide formulations tested were serial diluted (v/v) with sterile 0.9% NaCI. Each dilution was mixed v/v with processed sperm (100 ⁇ L/100 ⁇ L or 50 ⁇ L/50 ⁇ L, depending on the original sperm concentration and volume).
  • the first dilution (1/1) corresponds to the mixing of one volume of sperm suspension with one volume of pure CSSOL1 or 1 mg/mL octoxynol-9.
  • Dilution 1/2 corresponds to the mixing of one volume of sperm suspension with one volume of half-strength CSSOL1or half-strength 1 mg/mL octoxynol-9, and so on.
  • This test consisted of mixing sperm suspensions with two dyes (Eosin and Negrosin). The brightirefringent cells were ticked as viable, all the others (partial or total brownish coloration) as dead. This test was conducted on visually immobilized sperm.
  • Treated sperms were re-suspended in culture medium (1 v/20 v) for 15 minutes, then pelleted down by centrifugation (2000 RPM-200-300 g). The supernatant was carefully removed (pipette) and the pellet re-suspended in ⁇ 100 ⁇ L of remaining liquid. The percentage of motile cells was then recorded as described above.
  • Solution B3 Ingredient % wt Water 96.40 Copper sulfate pentahydrate 1.10 Acetic acid 1.34 Sodium silicate solution 1.16
  • Ortho-gynol® contains Octoxinol-9 at a concentration of 10 mg/g. The dilutions tested were made in 0.9% NaCl from the 1 mg/mL working solution.
  • M Motility—percentage indicates the proportion of motile cells, +and—indicate the average quality of this motility, ranging from ⁇ (low, inefficient motility. The cells move/spin on themselves but not forward) to ++++(very quick forward movement). Cells tagged ⁇ are considered incapable of fertilization.
  • V Viability—percentage indicates the proportion of viable cells as defined above.
  • Resuscitation describes the motility of the cells following the resuscitation procedure described above.
  • the percentage indicates the proportion of motile cells.
  • the average quality of this motility is ranked from ⁇ to ++++, as described above.
  • the first effective spermicidal dilution is that which achieves 0% motility or inefficient motility ( ⁇ ) of sperm.
  • TABLE 3 Comparative spermicidal activity of CSSOL1-pH 4 and Ortho-gynol (Donor A) Ortho-gynol ® [Octoxinol-9] CSSOL1 pH 4 (1 mg/mL) Dilution 5 min 15 min 5 min 15 min 1/1 M: 0% M: nd M: 0% M: nd V: ⁇ 0% V: 0% V: ⁇ 0% V: 0% 1/2 M: 0% M: nd M: 0% M: nd V: 0% V: nd V: 0% V: nd 1/4 M: 0% M: 0% M: ⁇ 50%, ⁇ M: 0% V: 80% V: 65% V: ⁇ 50% V: ⁇ 0% 1/8 M: 50%, ⁇ M: 35%, ⁇ M: >80%, +++ M: >50%, ++ V:

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US10/590,070 2004-02-16 2005-02-16 Spermicidal preparations and uses thereof Abandoned US20070116745A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AU20049007-19 2004-02-16
AU2004900719A AU2004900719A0 (en) 2004-02-16 Sperm-Active Preparations and Uses Thereof
PCT/AU2005/000197 WO2005077387A1 (fr) 2004-02-16 2005-02-16 Preparations spermicides et utilisations de celles-ci

Publications (1)

Publication Number Publication Date
US20070116745A1 true US20070116745A1 (en) 2007-05-24

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ID=34842350

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Application Number Title Priority Date Filing Date
US10/590,070 Abandoned US20070116745A1 (en) 2004-02-16 2005-02-16 Spermicidal preparations and uses thereof

Country Status (3)

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US (1) US20070116745A1 (fr)
EP (1) EP1715874A4 (fr)
WO (1) WO2005077387A1 (fr)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61503003A (ja) * 1984-04-19 1986-12-25 ユニバ−シテイ−　オブ　クイ−ンスランド 避妊方法、避妊用製剤及び避妊具
JP2875888B2 (ja) * 1991-10-17 1999-03-31 シーン バイオテクノロジー ピーティーワイ エルティーディー 殺虫・殺菌剤
AUPP068497A0 (en) * 1997-12-02 1998-01-08 Sheen Biotechnology Pty Ltd Use of copper for the control of legionella
AUPS099202A0 (en) * 2002-03-08 2002-04-11 Conve Ltd Use of copper silicate and zinc silicate for controlling microbes
AUPS179302A0 (en) * 2002-04-17 2002-05-30 Conve Ltd Use of topical compositions for the control of microbial diseases of the nail

Also Published As

Publication number Publication date
EP1715874A1 (fr) 2006-11-02
EP1715874A4 (fr) 2008-06-04
WO2005077387A1 (fr) 2005-08-25

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AS Assignment

Owner name: CONVE LTD., AUSTRALIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DAWSON, JOHN;REEL/FRAME:018501/0873

Effective date: 20060811

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION